SMAD4 and hereditary hemorrhagic telangiectasia: Altogether, this paper concludes that whole gene sequencing, not just coding regions, of ENG, ACVRL1/ALK1, and depending on the phenotype, even of Smad4 and BMP9, may reveal that non-coding regions play a larger role in HHT disease pathogenesis, which may help to cover the full range of genetic diagnoses in clinically diagnosed patients.